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Type: Artigo de periódico
Title: S-nitrosation Of The Insulin Receptor, Insulin Receptor Substrate 1, And Protein Kinase B/akt: A Novel Mechanism Of Insulin Resistance.
Author: Carvalho-Filho, Marco A
Ueno, Mirian
Hirabara, Sandro M
Seabra, Amedea B
Carvalheira, José B C
de Oliveira, Marcelo G
Velloso, Lício A
Curi, Rui
Saad, Mario J A
Abstract: Evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance in muscle. Here, we investigated whether this insulin resistance could be mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway. Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor beta subunit (IRbeta) and protein kinase B/Akt (Akt) and reduced their kinase activity in muscle. Insulin receptor substrate (IRS)-1 was also rapidly S-nitrosated, and its expression was reduced after chronic GSNO treatment. In two distinct models of insulin resistance associated with enhanced iNOS expression-diet-induced obesity and the ob/ob diabetic mice-we observed enhanced S-nitrosation of IRbeta/IRS-1 and Akt in muscle. Reversal of S-nitrosation of these proteins by reducing iNOS expression yielded an improvement in insulin action in both animal models. Thus, S-nitrosation of proteins involved in insulin signal transduction is a novel molecular mechanism of iNOS-induced insulin resistance.
Subject: Animals
Insulin Receptor Substrate Proteins
Insulin Resistance
Mice, Inbred Nod
Muscle, Skeletal
Nitric Oxide
Nitro Compounds
Protein Processing, Post-translational
Protein-serine-threonine Kinases
Proto-oncogene Proteins
Proto-oncogene Proteins C-akt
Rats, Wistar
Receptor, Insulin
Citation: Diabetes. v. 54, n. 4, p. 959-67, 2005-Apr.
Rights: fechado
Date Issue: 2005
Appears in Collections:Unicamp - Artigos e Outros Documentos

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